The amount of urine voided in bed by children with enuresis.

INTRODUCTION: Enuretic children wet their beds either because of nocturnal polyuria or nocturnal detrusor overactivity. Polyuric children often respond to desmopressin, whereas children with nocturnal detrusor overactivity are often therapy resistant and may have low daytime voided volumes. It is logical to assume that the enuretic event in children with nocturnal polyuria occurs with a full bladder, i.e. with the enuretic voided volume (EVV) close to the child's expected bladder capacity (EBC) for his/her age. However, the EVV has only rarely been studied, and little is known about how it relates to case history, polyuria, or daytime bladder function. The aim of this study was to look at EVV and relate it to voiding chart data and treatment response. METHODS: Anamnestic data and voiding charts, including measurement of nocturnal urine production and EVV, in enuretic children with or without concomitant daytime incontinence attending a tertiary center were retrospectively reviewed. The EVV was analyzed and compared to anamnestic data, voiding chart data, and response to therapy in accordance with the guidelines of the International Children's Continence Society. RESULTS: Data were available for 220 children (age 5-24, median 9), 40 of whom were girls. The prevalence of previous or present daytime incontinence was 42.4%, and 50.5% sometimes experienced urgency. The average EVV was 54.9 ± 32.8% of EBC. EVV correlated highly significantly to nocturnal urine production (p < 0.001). Still, EVV ≥ EBC was observed in only 16 children. EVV was slightly larger in girls (p = 0.013) and in children with urgency (p = 0.034), but there were no significant EVV differences between children responding or not responding to antidiuretic, anticholinergic, or antidepressant therapy. Relevant data are summarized in the Table below. DISCUSSION: Case history and daytime voiding chart data give very little information about nocturnal bladder function. The EVV is strongly influenced by nocturnal urine production but only rarely reaches up to a level close to or exceeding the EBC. The enuretic event only very rarely represents the emptying of a full bladder. Thus, a component of nocturnal detrusor overactivity can be assumed to be present in almost all enuretic children, even in children with nocturnal polyuria. The value of the EVV is limited in predicting response to therapy.

Reassuringly low carriage of enteropathogens among healthy Swedish children in day care centres.

OBJECTIVES: Infectious gastroenteritis is one of the most common diseases among children and has a considerable impact on health and socio-economy. Day care centres are high-risk environments for infections. The aim of this study was to investigate if asymptomatic preschool children constitute a reservoir for potential enteropathogens. STUDY DESIGN: In total, 438 individual diapers were collected from day care centres in Uppsala, Sweden, during spring and autumn, and molecular techniques were used to estimate the prevalence of asymptomatic carriage of multiple enteropathogens. METHODS: Faecal samples were analysed with multiplex polymerase chain reaction (PCR) (xTAG® Gastrointestinal Pathogen Panel; Luminex Corporation, Toronto, Canada) targeting 21 different pathogens. Samples with a median fluorescence intensity above threshold were re-analysed with a second PCR assay. RESULTS: Sixteen of the 438 samples were positive for enteropathogens, 1.6% for enteric adenovirus, 0.7% for Campylobacter spp., and 0.7% for norovirus. CONCLUSIONS: Preschool children in Uppsala constitute a limited reservoir for potential enteropathogens.

"Nobody asked us if we needed help": Swedish parents experiences of enuresis.

OBJECTIVE: To explore the everyday dilemmas of parents living with a child with nocturnal enuresis and to describe their support needs in relation to healthcare professionals. SUBJECTS AND METHODS: The study was conducted in 2011 in Uppsala County, Sweden. Parents of 13 children with enuresis, 10 mothers and three fathers, participated in qualitative semi-structured in-depth interviews, which were analysed using systematic text condensation. RESULTS: The analysis of the material resulted in six themes: enuresis is socially stigmatising and handicapping; all practices and home remedies are tested; it creates frustration in the family; protecting the child from gossip or teasing; support from healthcare providers would have helped; it's something we just have to live with. Two patterns of coping were identified: the Unworried wet-bed-fixers and the Anxious night-launderers. CONCLUSION: Having a child with enuresis can be stressful for parents, although they tried hard not to blame their child. Because parents can feel reluctant to bring up enuresis themselves, they want child health nurses to routinely raise the issue of bedwetting at the yearly check-up. Parents' information needs included causes of and available treatment options for enuresis as well as access to aids and other support for affected families.

Lower urinary tract function in childhood; normal development and common functional disturbances.

This review aims to provide researchers and clinicians involved with the adult lower urinary tract with background knowledge regarding the early development of bladder function and its most common disturbances in childhood. Bladder development begins in weeks 4-6 and the detrusor muscle is formed during weeks 9-12 of gestation. Higher CNS centres are involved in micturition at birth, and the infant usually wakes up, at least briefly, to void. Voiding during the first years of life is often incomplete, owing to detrusor-sphincter dyscoordination, but this disappears when bladder control is attained. Approximately 5-10% of 7-year-old children suffer from daytime incontinence and/or nocturnal enuresis, and a few per cent of them will not outgrow it. Daytime incontinence in childhood is usually attributable to detrusor overactivity, although it is unclear to what extent it is the detrusor or the micturition reflex per se that is overactive. Enuresis - nocturnal incontinence - is caused by either nocturnal polyuria and/or nocturnal detrusor overactivity, in both cases combined with high arousal thresholds. Bladder problems in childhood constitute a risk factor for the development or persistence of bladder problems in adulthood.

The role of sleep and arousal in nocturnal enuresis.

AIM: To review what is known about the role of sleep and arousal mechanisms in the pathogenesis of nocturnal enuresis. METHODS: A review of the literature was carried out. RESULTS: The sleep of enuretic children, although polysomnographically quite normal, is exceedingly "deep"; that is enuretic children have high arousal thresholds. Apart from some overlap between enuresis and the (other) classic parasomnias, the sleep of enuretic children is no more problematic than that of the general population. Recently, the exciting possibility has arisen that the low arousability of enuretic children may be linked to the autonomous nervous system and to disturbances in the upper pons. CONCLUSIONS: Enuresis is not just a nocturnal problem but a disorder of sleep. The high arousal threshold is one of three major pathogenetic factors in enuresis-nocturnal polyuria and detrusor hyperactivity being the other two.

Enuresis, sleep and desmopressin treatment.

AIM: To detect effects of desmopressin on sleep in enuretic children and to look for polysomnographical differences between responders and non-responders to desmopressin treatment. METHODS: Twenty-one children with primary nocturnal enuresis were examined polysomnographically before treatment. All but one of the children then received treatment with desmopressin in standard dosage, and the response was documented. Seven of the children underwent a second polysomnographic registration while on treatment. RESULTS: The time interval (+/- 1 SD) between sleep onset and the enuretic episode was 92 +/- 67 min without medication and 372 +/- 157 min when desmopressin was given (p = 0.003). Standard polysomnographic variables were not affected by the drug. Ten children were desmopressin responders and 10 were non-responders. The total sleep time was 455 +/- 56 min in the former and 408 +/- 31 min in the latter group (p = 0.04). The responders spent 27.4 +/- 5.5% of their total sleep time in rapid eye movement sleep, compared with 18.2 +/- 6.5% in the non-responder group (p = 0.004). CONCLUSION: Desmopressin has no major effects on sleep as such but does delay bladder emptying. Enuretic children responding to desmopressin treatment have more rapid eye movement sleep than therapy-resistant children.

Vasopressin and hypercalciuria in enuresis: a reappraisal.

OBJECTIVE: To test the hypotheses that vasopressin deficiency or hypercalciuria are important in polyuric and non-polyuric bedwetting, as nocturnal polyuria is a pathogenetic factor in enuresis responsive to antidiuretic therapy with desmopressin. SUBJECTS AND METHODS: Vasopressin deficiency has been implicated as a cause of nocturnal polyuria, but measurements of vasopressin in plasma have given contradictory results, because the hormone is released in pulses. Urinary levels reflect the secretion over longer periods. Hypercalciuria has also been proposed as a pathogenetic factor. Twenty-eight enuretic children who responded to desmopressin therapy with or without added anticholinergic agents (diuresis-dependent enuresis, DE), 15 children with therapy-resistant enuresis (not diuresis-dependent, NDE) and 51 continent controls were assessed. Urinary vasopressin, calcium and osmolality were measured in the morning after a 12-h thirst provocation. Urine production was recorded for 2 days. RESULTS: Because most data were not normally distributed, the values are expressed as the median (range). There were no differences in urine osmolality; i.e. con-trols 919 (636-1232), DE 849 (462-1149), NDE 968 (664-1191) mOsml/kg); vasopressin, controls 34 (8-983), DE 26 (9-295), NDE 50 (9-116) pmol/L; or calcium excretion (expressed as the calcium/creatinine ratio), controls 0.16 (0.01-0.71), DE 0.14 (0.04-0.67), and NDE 0.23 (0.03-0.69). The DE group produced more urine, at 18.4 (9.2-52.5) mL/kg/day, than the other groups, i.e. control 12.7 (8.3-42.8) and NDE 12.1 (6.3-36.8) mL/kg/day (P = 0.008). CONCLUSION: All enuretic children with nocturnal polyuria do not have vasopressin deficiency. The urinary calcium excretion does not differ between enuretic and dry children.

Oxybutynin, desmopressin and enuresis.

PURPOSE: A review of the scarce literature concerning oxybutynin treatment for nocturnal enuresis reveals that its success is greatest when enuresis is combined with daytime incontinence. The renal and bladder related characteristics of children with monosymptomatic enuresis responsive to oxybutynin were evaluated. MATERIALS AND METHODS: Renal concentrating capacity and functional bladder capacity were compared between 55 dry children who served as controls, and children with monosymptomatic enuresis who responded to desmopressin only (group 1, 27), oxybutynin only (group 2, 11), combination desmopressin and oxybutynin (group 3, 7) or were resistant to all treatment alternatives (group 4, 23). RESULTS: Renal concentrating capacity was lowest in groups 1 and 3 (939 +/- 147 mOsm./kg. controls, 856 +/- 158 group 1, 1,073 +/- 71 group 2, 762 +/- 119 group 3 and 970 +/- 146 group 4; p <0.01), whereas they had high urinary output (15.4 +/- 73.4 ml./kg. per hour controls, 22.2 +/- 10.2 group 1, 13.5 +/- 4.3 group 2, 21.5 +/- 11.2 group 3 and 15.0 +/- 6.9 group 4; p <0.01). Forced functional bladder capacity of that expected for age was lowest in groups 2 to 4 (107 +/- 43% controls, 88 +/- 43 group 1, 71 +/- 25 group 2, 68 +/- 22 group 3 and 59 +/- 22 group 4; p <0.01). CONCLUSIONS: Children responding to oxybutynin have small bladders and probably hyperactive detrusors, whereas those responding to desmopressin or who need both drugs to achieve dryness have polyuria.

[Alarm defends its position. Comments to meta-analysis of alarm treatment of nocturnal enuresis]. / Kisslarmet försvarar sin plats. Kommentar till en metaanalys av larmbehandling vid nattväta.

Glazener and Evans have, on behalf of the Cochrane Library, performed a systematic literature review of alarm interventions in nocturnal enuresis. An extensive, and probably exhaustive, search yielded 22 studies which were of sufficient methodological quality and in which the enuresis alarm was included as one treatment alternative. From these studies it could be concluded that 1) the enuresis alarm is clearly more effective than non-treatment, 2) different types of enuresis alarms do not differ significantly as regards efficacy, and 3) alarm treatment is not clearly superior or inferior to pharmacological treatment.

Bladder capacity and renal concentrating ability in enuresis: pathogenic implications.

PURPOSE: We compared bladder volume and renal concentrating capacity in dry children and 2 distinct groups of children with enuresis to hypothesize about the pathogenesis of various types of enuresis. MATERIALS AND METHODS: A total of 55 dry children and 100 with enuresis underwent an overnight thirst provocation test to assess renal concentrating capacity and completed a 2-day voiding chart to assess functional bladder capacity. The enuretic children were subdivided into 27 desmopressin responders and 73 desmopressin nonresponders before study inclusion. RESULTS: The desmopressin responder group had lower average renal concentrating capacity +/-1 standard deviation than dry children and desmopressin responders (856 +/- 158 mOsm./kg. versus 939 +/- 147 and 962 +/- 151, respectively, p <0.05). Analogously average daytime urine production in the desmopressin responder group was greater than in dry children and desmopressin responders (22.2 +/- 10.2 ml./kg. body weight versus 15.4 +/- 7.3 and 15.3 +/- 7.2, respectively, p <0.01). Average functional bladder capacity expected for age was less in desmopressin nonresponders than in dry children and responders (52.2% +/- 19.9% versus 79.2% +/- 30.4% and 69.5% +/- 25.7%, respectively, p <0.001). CONCLUSIONS: Desmopressin responders produced larger amounts of less concentrated urine than the other children, while desmopressin nonresponders had smaller bladder capacity than the other groups. These results support the idea that enuretic children who respond favorably to desmopressin treatment have polyuria, whereas children with therapy resistant enuresis have detrusor hyperactivity.

Sleep habits and sleep problems among a community sample of schoolchildren.

UNLABELLED: Sleep habits, sleep problems and subjective depth of sleep among 1413 schoolchildren aged 6.2-10.9 y were examined via a questionnaire, answered by the child and parent together. Total sleep time was approximately 10.5 h, with no difference between the sexes. Of 887 children who reported that they were awoken at night, parents considered that 75% were superficial sleepers and 25% were deep sleepers. The prevalence of frequent insomnia, sleepwalking and daytime sleepiness was 13, 7 and 4%, respectively. Logistic regression analyses indicated that onset insomnia was associated with fear of sleeping alone, bone pains, hypnagogic myoclonias, rhythmic movement disorder, enuresis, nocturia, confusion when awoken at night, nightmares, bodily movements during sleep, interrupted sleep, daytime sleepiness and daytime headache or stomach ache. Somnambulism was associated with rhythmic movement disorder, somniloquy, spontaneous confused arousals, nocturia and confusion when awoken at night. Increased risk of daytime sleepiness was found among children with fear of sleeping alone, onset insomnia, rhythmic movement disorder, spontaneous confused arousals, snoring, confusion when awoken, nightmares, bodily movements during sleep and headache or stomach ache. CONCLUSION: The results support the notion that onset insomnia is a problem with a predominantly psychological and behavioural background, while sleepwalking is a disorder of arousal without major psychological implications. The mechanisms behind daytime sleepiness seem to be multifactorial.

Enuresis--background and treatment.

Nocturnal urinary continence is dependent on 3 factors: 1) nocturnal urine production, 2) nocturnal bladder function and 3) sleep and arousal mechanisms. Any child will suffer from nocturnal enuresis if more urine is produced than can be contained in the bladder or if the detrusor is hyperactive, provided that he or she is not awakened by the imminent bladder contraction. Urine production is regulated by fluid intake and several interrelated renal, hormonal and neural factors, foremost of which are vasopressin, renin, angiotensin and the sympathetic nervous system. Detrusor function is governed by the autonomic nervous system which under ideal conditions is under central nervous control. Arousal from sleep is dependent on the reticular activating system, a diffuse neural network that translates sensory input into arousal stimuli via brain stem noradrenergic neurons. Disturbances in nocturnal urine production, bladder function and arousal mechanisms have all been firmly implicated as pathogenetic factors in nocturnal enuresis. The group of enuretic children are, however, pathogenetically heterogeneous, and two main types can be discerned: 1) Diuresis-dependent enuresis - these children void because of excessive nocturnal urine production and impaired arousal mechanisms. 2) Detrusor-dependent enuresis - these children void because of nocturnal detrusor hyperactivity and impaired arousal mechanisms. The main clinical difference between the two groups is that desmopressin is usually effective in the former but not in the latter. There are two first-line therapies in nocturnal enuresis: the enuresis alarm and desmopressin medication. Promising second-line treatments include anticholinergic drugs, urotherapy and treatment of occult constipation.

Desmopressin resistant enuresis: pathogenetic and therapeutic considerations.

PURPOSE: We tested the role of the bladder in the pathogenesis of desmopressin resistant enuresis by evaluating the influence of urine production on the timing of the enuretic event and the response to anticholinergic medication. MATERIALS AND METHODS: We gave 33 children with monosymptomatic nocturnal enuresis resistant to the standard 0.4 mg. oral dose of desmopressin 0.4 and 0.8 mg. desmopressin and placebo tablets for 5 nights each in a double-blind crossover fashion. The time of enuresis or nocturia was documented. All 9 children who had at least 1 dry treatment period during the randomized portion of the study then received open label treatment with 0.8 mg. desmopressin. Nonresponders to this regimen and the remainder of the children were offered anticholinergic treatment. RESULTS: Average time between bedtime and voiding was 5.0, 5.6 and 5.0 hours during the nights with placebo, and 0.4 and 0.8 mg. desmopressin, respectively (p = 0.12). Of the 9 children subsequently treated with 0.8 mg. desmopressin 5 became completely dry. Of the remaining 28 children given anticholinergic treatment 20 responded. CONCLUSIONS: Antidiuresis does not delay the enuretic event in children with desmopressin resistant enuresis. This finding and the favorable response to anticholinergic medication favor the hypothesis that these children have nocturnal bladder instability. A subgroup of enuretic children responds to high but not normal doses of desmopressin.

Depth of sleep and sleep habits among enuretic and incontinent children.

In order to evaluate differences in sleep factors between children with wetting problems and dry children, questionnaire data were obtained from 1,413 schoolchildren between the ages of 6 and 10 y. The analyses were performed using logistic regression, and adjusted odds ratios (ORs) were calculated to approximate the relative risk. Current enuresis was associated with a subjectively high arousal threshold, pavor nocturnus, nocturia and confusion when awoken from sleep (ORs 2.7, 2.4, 2.1 and 3.4, respectively), whereas children with current incontinence often experienced bedtime fears, onset insomnia or nocturia (ORs 2.4, 2.3 and 2.7, respectively). Children exhibiting urinary urgency were overrepresented among both children with current enuresis (OR 2.5) and those with current incontinence (OR 17.2). It is concluded that impaired arousal mechanisms and bladder instability are aetiological factors underlying nocturnal enuresis.

Sleep of children with enuresis: a polysomnographic study.

OBJECTIVE: To evaluate relationships between bladder voiding and sleep in children with enuresis. METHODS: Polysomnographic recordings were obtained from 25 children, aged 7 to 17 years, with monosymptomatic nocturnal enuresis. During 52 recorded nights, 37 enuretic events were detected. Responders (n = 7) and nonresponders (n = 16) to desmopressin treatment were compared. RESULTS: The mean latency between sleep onset and the first bladder voiding was 3 hours 20 minutes (SD = 2 hours 5 minutes). The number of voidings were 19, 7, 10, and 1 occurring during stages 2, 3, and 4, and rapid-eye movement sleep, respectively. Desmopressin responders were found to void during the early or late part of the night, whereas the voidings of the nonresponders were dispersed evenly throughout the night (chi2 = 8.09). CONCLUSIONS: The enuretic event is a predominantly non-rapid eye movement sleep phenomenon. Responders and nonresponders to desmopressin treatment void during different parts of the night.

Osmoregulation and desmopressin pharmacokinetics in enuretic children.

OBJECTIVE: The aim was to compare responders and nonresponders to antienuretic treatment with desmopressin with respect to pharmacokinetics and renal effects of the drug. METHODS: Twelve children, aged 7.6 to 16.2 years, with nocturnal enuresis were examined. Six patients were nonresponders and 6 were responders to desmopressin treatment. The children were given 2 mg of desmopressin intravenously and plasma concentrations of the drug were monitored overnight. Urine parameters were followed for 24 hours after desmopressin administration. Ten patients also underwent a thirst provocation test. RESULTS: Desmopressin pharmacokinetics did not differ between the groups. Neither nocturnal urine production nor morning urine osmolality after desmopressin injection differed between responders and nonresponders, whereas the responders produced significantly larger amounts of significantly less concentrated urine during the day after the injection compared with the nonresponders (urine production, 2.02 +/- 0.84 and 0.77 +/- 0.20 mL/kg/h; urine osmolality, 558 +/- 271 and 883 +/- 134 mOsm/kg). Nonresponders voided with smaller bladder volumes (2.43 +/- 0.68 mL/kg body weight) than responders (4.70 +/- 1.21 mL/kg). The responders produced significantly less concentrated urine than the nonresponders during the thirst provocation test (607 +/- 185 and 922 +/- 217 mOsm/kg, respectively). CONCLUSION: Intravenous desmopressin pharmacokinetics and desmopressin renal effects did not differ between responders and nonresponders to desmopressin treatment. Nonresponders had a smaller spontaneous bladder capacity and responders produced less concentrated urine.

Desmopressin in the treatment of severe nocturnal enuresis in adolescents--a 7-year follow-up study.

OBJECTIVES: To evaluate the role of long-term oral desmopressin (over a 7-year follow-up) in refractory enuretics, particularly in assessing the potential curative effect, and to analyse the results for specific types of patient to obtain clues about possible mechanisms of cure. PATIENTS AND METHODS: The effect of oral desmopressin was investigated in 25 adolescents (aged 11-21 years) with severe monosymptomatic nocturnal enuresis. The long-term study consisted of two 12-week treatment periods, with the efficacy of the drug assessed as the reduction in the number of wet nights per week. Subsequently, the patients were followed-up for up to 7 years. Close contact was maintained with the families over this period ('good doctoring' approach). At 3-, 5- and 7-year intervals after completing the study, patients were assessed for dryness, frequency, treatment and sleeping habits, using postal questionnaires and telephone follow-up. RESULTS: At the end of the long-term study, 35% of the patients remained dry without therapy. Within 2 years of ending treatment, 15 patients were dry, compared with an expected estimate of six by spontaneous resolution, and after 7 years, 19 patients were cured. Nocturia occurred in 75% of the enuretic patients but in only 5% of the healthy controls. CONCLUSIONS: Active treatment of primary nocturnal enuresis with oral desmopressin has a clinically significant effect on the cure rate, which is maintained after ceasing therapy. The cure rate was higher than would be expected from spontaneous recovery alone during the first 2 years of the study and there was a significant further increase in the cure rate 7 years after ending therapy, again greater than the expected spontaneous cure rate. There also seemed to be a better response to treatment when it was prolonged. Furthermore, this therapy is safe when administered in the long-term.

Sleep and night-time behaviour of enuretics and non-enuretics.

OBJECTIVE: To investigate connections between nocturnal enuresis and sleep factors such as the subjective depth of sleep and classical parasomnias. PATIENTS, SUBJECTS AND METHODS: One hundred school children aged 6-10 years answered a questionnaire, with their parents, and the same questions were asked of a group of 29 children of the same age suffering from severe nocturnal enuresis. RESULTS: There were significant differences in arousability, with the enuretic group being 'deep sleepers', and in the prevalence of onset insomnia, nightmares, interrupted sleep and bedtime struggles, which were all less common among the enuretics. The prevalence of classical parasomnias did not differ between the groups. CONCLUSION: A high arousal threshold is one of the pathogenetic factors underlying nocturnal enuresis and we propose that this group of therapy-resistant enuretic children might not only sleep more deeply than their nonenuretic peers, but perhaps have 'better' sleep.